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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 727239, 9 pages
Research Article

Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/ in Skinned Myocardium

1Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, P.O. Box 245217, Tucson, AZ 85724, USA
2Department of Food Science and Technology, National Fisheries University, 2-7-1 Nagata-honmachi, Shimonoseki, Yamaguchi 759-6595, Japan

Received 6 December 2009; Accepted 15 January 2010

Academic Editor: Aikaterini Kontrogianni-Konstantopoulos

Copyright © 2010 Hideto Fukushima et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a “viscous break” that is on during diastole and off during systole.